Structural Biochemistry and Mechanisms

Structural Biochemistry and Mechanisms

The recent years of whole genome studies have enforced a view, in which most cellular constituents do not act in isolation, but as part of large assemblies. A large spectrum of biological reactions and tasks essential for the survival of cells are performed by these macromolecular complexes, also referred to as molecular machines. These biochemically labile assemblies are composed of either protein only, or proteins bound to nucleic acids (DNA or RNA). Prominent examples are the proteasome, the fatty acid synthase, the nucleosome, the ribosome, and the spliceosome. As cellular homeostasis is governed by macromolecular complex function, their mis-function is also a central cause for human disease, making the in-depth study of functional mechanisms essential for the investigation of disease etiology.

In our research, we apply mechanistic biochemistry and X-ray crystallography to study large macromolecular complexes involved in proteostasis and fatty acid metabolism. Owing to the labile nature and complexity of interrogating these molecular machines, we are engaged in the development of biochemical tools to purify and stabilize them, as well as arrest them in distinct functional states. We also develop methods for X-ray data collection, phasing, structure determination, and refinement of large complexes. To study dynamic aspects of their function we apply time-resolved approaches.

 

Press Releases

Holger Stark and his team have broken a crucial resolution barrier in cryo-electron microscopy. The scientists succeeded in observing single atoms in a protein structure and taking the sharpest images ever with this method. Such unprecedented details are essential to understand how proteins perform their work or cause diseases in the living cell. The technique can in future also be used to develop active compounds for new drugs. more

Tuberculosis still represents the infectious disease with the highest fatality numbers and is caused by mycobacteria. The fatty acid biosynthetic factory is an important target in the fight against this infectious bacterium. Göttingen researchers have now discovered a protein that commands and controls FAS function. This finding not only opens up new therapeutic venues, particularly against tuberculosis. In biotechnological applications this new control unit enables the generation of tailor-made fatty acid synthases.  more

Ribosomal quality control

September 29, 2016

Formation of macromolecular machines within cells is often a complicated endeavor. Biochemists of the University of Würzburg and the MPI for Biophysical Chemistry have now unraveled new details of these processes. They show that cells invest a great deal of effort into preventing production errors. more

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